Viral infections of the CNS and the host immunological reaction to them are capable of producing a wide variety of clinical and pathological states, many of which bear few of the traditional hallmarks of acute inflammatory brain fevers. Some are "slow infections", measuring incubation period and disease duration from months to many years. Some attack restricted CNS cell populations producing such varied pathologic conditions as demyelination, hydrocephalus, or spongioform states. Multiple sclerosis displays many characteristics suggestive of a chronic viral or immunological disorder including cerebrospinal fluid changes similar to subacute sclerosing panencephalitis and pathologic changes reminiscent of experimental allergic encephalomyelitis. This Center Grant request outlines studies of human clinical and pathological material from humans designed to develop knowledge of the cause and pathogenesis of multiple sclerosis, Creutzfeldt-Jakob disease and other human CNS diseases linked to virus infections. It also describes studies of several animal models chosen to elucidate mechanisms by which viruses produce CNS disease. Numerous serologic, tissue culture, cellular immune, and molecular biological methods will be employed. Electron microscopic, virologic and radioimmunoassay techniques are also proposed. The six investigators initiating this request have varied but interrelated interests and areas of expertise allowing for essential collaboration to achieve the objectives of the grant.